Antiangiogenesis in myelodysplastic syndrome.

One of the best examples of the bench-to-bedside paradigm in recent years could be the myelodysplastic syndromes (MDS). New insight into the pathophysiology of this heterogeneous group of diseases has led to relevant clinical changes. We have now the World Health Organization classification of MDS, the International Prognostic Score System to evaluate risk according to some clinical and laboratory parameters, and the approval by most of the regulatory agencies around the world of 5-azacitidine, decitabine and lenalidomide to treat MDS patients. In the last decade a robust body of evidence supports the importance of angiogenesis and angiogenesis related molecules as having a key role in the pathophysiology of hematologic malignancies including of MDS. A group of researchers around the globe is testing drugs with angiogenesis-regulatory characteristics with some success. Experience from those trials has shown angiogenesis in MDS as a dynamic process, a "moving target". Lenalidomide hit one and, although experience is being gained the complete answer is not there yet. Combinations of drugs with different mechanisms of actions are options that need to be tested. Herein we present some of the accumulated experience with these novel antiangiogenic-drugs.

Moderate and severe neutropenia in patients with systemic lupus erythematosus.

OBJECTIVES: Neutropenia is an uncommon albeit relevant finding in patients with systemic lupus erythematosus (SLE). It has been ascribed to several aetiologies and represents a challenging dilemma in which clinical findings, laboratory data and medication history must be carefully evaluated. The aim of this work was to review the cases of moderate and severe neutropenia in our cohort of SLE patients in order to identify predisposing factors, clinical outcomes and related prognostic implications. METHODS: Thirty-three cases of neutropenia (neutrophil count <1000/microl) in patients with SLE were included. Sixty-five age- and sex-matched patients with SLE served as controls. Information was obtained by medical chart review. Statistical analyses included descriptive statistics, Student's t-test, paired t-test, chi 2 or Fisher's exact test, and logistic regression. RESULTS: Baseline characteristics did not differ between groups. Use of concomitant medications and immunosuppressive drugs, as well as history of thrombocytopenia and central nervous system involvement, were associated with an increased risk for developing neutropenia. Along with neutropenia, cases had lower haemoglobin and platelet values and higher levels of liver enzymes. Moreover, disease activity was lower than in controls. One month after the neutropenia event, leucocyte and total granulocyte counts were still lower in patients than in controls. Mortality did not differ between patients with neutropenia and controls. CONCLUSIONS: Most episodes of severe granulocytopenia in SLE patients occur as part of drug toxicity-induced medullar hypoplasia.

DNA sequencing of HLA-B alleles in Mexican patients with Takayasu arteritis.

Takayasu arteritis (TA) is characterized by a 'pulseless' condition and occurs frequently in young females from Asian and South American countries. It has been associated with Mayor Histocompatibility Complex (MHC) genes in different populations. Recent data indicate direct participation of HLA-B alleles in the susceptibility to the disease. This fact was explored in an associative study with TA to establish if some region in the exon 2, intron 2 or in the exon 3 of HLA-B alleles is common in the alleles associated with TA and at the same time to know if a specific sequence or an epitope, more than an allele, would be responsible for the susceptibility to this vasculitis. We studied HLA-B alleles of 12 Mexican patients with TA using PCR-SSP and sequencing. The analysis by PCR-SSP in 12 patients showed that five of them showed the B*15 allele, three the B*40 allele and two the B*39 allele, the remaining two presented the B*44 allele. Sequence analysis enabled us to define that the B*39 subtypes are B*3908; B*15 subtypes are B*1510, B*1515, B*1522 and B*1531; and the B*40 subtypes are B*4005 and B*4008. An individual with B*51 (B*5107) and another with B*52 (B*5201) alleles were also identified. The sequences of the intron 2 seem be heterogeneous. Analysis at the 63 and 67 positions of HLA-B alleles showed that 9 of them have similarity in some of these positions with the residues detected in the B*5201 and B*3902 alleles associated with TA in Asian populations. The results indicate that there is heterogeneity in the alleles associated with TA in Mexicans but, in spite of that heterogeneity, the alleles associates can be separated into three groups: B*39, B*15 and B*40, whose subtypes are rare and apparently of recent generation in Mexico, probably by recombination events at intron 2 level. The sequences analysis also shows that most of the alleles detected in the Mexican patients share two epitopes described in the susceptibility alleles in Asian populations, suggesting that these epitopes could be responsible for the susceptibility to develop the disease in spite of the allele in which are found.